Comprehensive genomic sequencing detects important genetic differences between right-sided and left-sided colorectal cancer

Shimada, Yasuhiro; Kameyama, Hitoshi; Nagahashi, Masayuki; Ichikawa, Hiroshi; Muneoka, Yojiro; Yagi, Ryoma; Tajima, Yosuke; Okamura, Takuma; Nakano, Masato; Sakata, Jun; Kobayashi, Takashi; Nogami, Hitoshi; Maruyama, Satoshi; Takii, Yasumasa; Hayashida, Tetsu; Takaishi, Hiromasa; Kitagawa, Yuko; Oki, Eiji; Konishi, Tsuyoshi; Ishida, Fumio; Kudo, Shin Ei; Ring, Jennifer E.; Protopopov, Alexei; Lyle, Stephen; Ling, Yiwei; Okuda, Shujiro; Ishikawa, Takashi; Akazawa, Kohei; Takabe, Kazuaki; Wakai, Toshifumi

doi:10.18632/oncotarget.20510

Cited by 25 publications

(22 citation statements)

References 29 publications

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“…The relationship between colonic location and differential clinical and molecular features of CRC has been widely established, and the same seems to apply to SCRC (2, 7, 9). Our division of SCRC into categories according to clonality and colon location of the tumors within the same patient showed a smaller proportion of SCRC cases in the right colon that were mainly monoclonal, as opposed to the higher rate of SCRCs in the left colon, which were mainly polyclonal.…”

Section: Discussionmentioning

confidence: 99%

Redefining synchronous colorectal cancers based on tumor clonality

Perea

Garcı́a

Corchete

et al. 2018

Intl Journal of Cancer

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To analyze the possible clonal origin of a part of Synchronous colorectal cancer (SCRC), we studied 104 paired-SCRCs from 52 consecutive patients without hereditary forms of CRC. We used a Single-Nucleotide Polymorphism array to characterize the genomic profiles, and subsequently used a statistical application to define them according to clonality within the same individual. We categorized the ensuing groups according to colonic location to identify differential phenotypes. The SCRC Monoclonal group (M) (19 cases) was divided into Monosegmental (MM) and Pancolonic (MP) groups. The SCRC Polyclonal group (P) (33 cases) was also divided into Monosegmental (PM) and Pancolonic (PP), the first exhibiting preference for left colon. The MM group showed a high rate of mucinous tumors, the lowest mean-number of tumors and associated-polyps, and the worst prognosis. The MP group included the largest mean-number of associated-polyps, best prognosis and familial cancer component. The PM group seemed to be a "frontier" group. Finally, the PP group also exhibited a mucin component, the highest mean-number of tumors (4.6) compared with the mean-number of polyps (7.7), poor prognosis and sporadic cases. Most relevant differential genomic regions within M groups were gains on 1q24 and 8q24, and deletions on 1p21 and 1p23 for MM, while within P were the gains on 7q36 and deletions on 1p36 for PM. The statistical application employed seems to define clonality more accurately in SCRC -more likely to be polyclonal in origin-, and together with the tumor locations, helped us to configure a classification with prognostic and clinical value.

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Section: Discussionmentioning

confidence: 99%

Redefining synchronous colorectal cancers based on tumor clonality

Perea

Garcı́a

Corchete

et al. 2018

Intl Journal of Cancer

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“…As previously described (15,(31)(32)(33)(34), formalin-fixed, paraffinembedded (FFPE) samples were used for next-generation sequencing (NGS), and genetic alterations, including RNF43, were evaluated. Briefly, hematoxylin and eosin-stained sections were used to assess tumor content, to ensure that >50% tumor content was present.…”

Section: Comprehensive Genomic Sequence Analysis Of Primary Tumorsmentioning

confidence: 99%

“…Primary tumor location was determined by operative findings. Cancer in the cecum, ascending colon, hepatic flexure, or transverse colon was classified as RCRC; while cancer in the splenic flexure, descending colon, sigmoid colon, rectosigmoid, or rectum was classified as LCRC (15).…”

Section: Rnf43 Status and Clinicopathological Characteristicsmentioning

confidence: 99%

“…RCRC and LCRC have different clinicopathological and molecular characteristics. RCRC is generally characterized by being more common in women, and associated with Lynch syndrome, sessile serrated adenoma/polyp (SSA/P), mitogen-activated protein kinase signaling, microsatellite instability-high (MSI-H), deficiency of mismatch repair genes, CpG island methylation, and KRAS and BRAF V600E mutations (11)(12)(13)(14)(15). LCRC is more common in men, and associated with familial adenomatous polyposis syndrome, traditional serrated adenoma (TSA), chromosomal instability, ERBB1 and ERBB2 amplifications, and APC, p53, and NRAS mutations (11)(12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

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RNF43 mutation is associated with aggressive tumor biology along with BRAF V600E mutation in right-sided colorectal cancer

et al. 2020

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Right-sided colorectal cancer (RCRC) demonstrates worse survival outcome compared with left-sided CRC (LCRC). Recently, the importance of RNF43 mutation and BRAF V600E mutation has been reported in the serrated neoplasia pathway, which is one of the precancerous lesions in RCRC. It was hypothesized that the clinical significance of RNF43 mutation differs according to primary tumor sidedness. To test this hypothesis, the clinicopathological characteristics and survival outcome of patients with RNF43 mutation in RCRC and LCRC were investigated. Stage I-IV CRC patients (n=201) were analyzed. Genetic alterations including RNF43 using a 415-gene panel were investigated. Clinicopathological characteristics between RNF43 wild-type and RNF43 mutanttype were analyzed. Moreover, RNF43 mutant-type was classified according to primary tumor sidedness, i.e., rightsided RNF43 mutant-type or left-sided RNF43 mutant-type, and the clinicopathological characteristics between the two groups were compared. RNF43 mutational prevalence, spectrum and frequency between our cohort and TCGA samples were compared. RNF43 mutation was observed in 27 out of 201 patients (13%). Multivariate analysis revealed that age (≥65), absence of venous invasion, and BRAF V600E mutation were independently associated with RNF43 mutation. Among the 27 patients with RNF43 mutation, 12 patients were right-sided RNF43 mutant-type and 15 left-sided RNF43 mutant-type. Right-sided RNF43 mutant-type was significantly associated with histopathological grade 3, presence of lymphatic invasion, APC wild, BRAF V600E mutation, microsatellite instability-high (MSI-H), and RNF43 nonsense/ frameshift mutation compared with left-sided RNF43 mutanttype. Similarly, RNF43 nonsense/frameshift mutations were more frequently observed in RCRC compared with LCRC in the TCGA cohort (P=0.042). Right-sided RNF43 mutant-type exhibited significantly worse overall survival than RNF43 wild-type and left-sided RNF43 mutant-type (P=0.001 and P=0.023, respectively) in stage IV disease. RNF43 mutation may be a distinct molecular subtype which is associated with aggressive tumor biology along with BRAF V600E mutation in RCRC.

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“…It is therefore important to consider geographic and ethnic differences when looking to understand the profile of genomic alterations, and apply NGS analysis to the development of therapies for Asian patients. Recently, we studied several types of solid cancers, including colorectal, gastric, lung, and breast cancer, in Japan utilizing NGS-based comprehensive genomic panel testing, 8,[11][12][13][14][15][16][17][18] and revealed some differences in genomic alterations between Asian and non-Asian populations.…”

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confidence: 99%

Next generation sequencing‐based gene panel tests for the management of solid tumors

et al. 2018

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Next generation sequencing (NGS) has been an invaluable tool to put genomic sequencing into clinical practice. The incorporation of clinically relevant target sequences into NGS‐based gene panel tests has generated practical diagnostic tools that enable individualized cancer‐patient care. The clinical utility of gene panel testing includes investigation of the genetic basis for an individual's response to therapy, such as signaling pathways associated with a response to specific therapies, microsatellite instability and a hypermutated phenotype, and deficiency in the DNA double‐strand break repair pathway. In this review, we describe the concept of precision cancer medicine using target sequences in gene panel tests as well as the importance of the control of sample quality in routine NGS‐based genomic testing. We describe geographic and ethnic differences in cancer genomes, and discuss issues that need to be addressed in the future based on our experiences in Japan.

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Comprehensive genomic sequencing detects important genetic differences between right-sided and left-sided colorectal cancer

Cited by 25 publications

References 29 publications

Redefining synchronous colorectal cancers based on tumor clonality

Redefining synchronous colorectal cancers based on tumor clonality

RNF43 mutation is associated with aggressive tumor biology along with BRAF V600E mutation in right-sided colorectal cancer

Next generation sequencing‐based gene panel tests for the management of solid tumors

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